This project will build on the very considerable progress that has been made in the past grant period in the analysis of the organization of the orbital and medial prefrontal cortex (OMPFC), and the thalamic and limbic areas that are connected with it. The OMPFC has been implicated in several important functions, including stimulus reward associations and the control of goal-directed behavior, but little has been known about the neural organization that might underlie such functions. In the previous grant period 24 architectonic areas were defined in the OMPFC, and sensory and limbic inputs to these areas were demonstrated, largely with retrograde axonal tracers. Three largely distinct networks of connections within the OMPFC were defined. In the next period anterograde axonal tracers will be used to continue the analysis of corticocortical connections within the OMPFC. Special emphasis will be placed on the termination of convergent inputs to architectonic areas in the central and rostral orbital cortex, and on laminar patterns of termination of feed-forward and feed-back connections. In addition, connections of the OMPFC with the hypothalamus and brainstem will be defined in order to clarify the control exerted by the OMPFC over visceral function. connections between the OMPFC and thalamic nuclei other than MD (e.g. the anteromedial and ventral anterior nuclei) will be defined with anterograde and retrograde axonal tracers. In most cases injections of at least four tracers will be made in each experiment, in order to obtain direct comparison of several different projections. The correlation between cortical areas in rats and monkeys will also be studied, with an analysis of cortico-cortical connections within the OMPFC of rats. In order to visualize the complex patterns of connections within the prefrontal cortex, computer methods will be developed to make 3-D reconstructions of the frontal cortex from plots of labeled cells and axons in serial sections. From these reconstructions unfolded 2-D maps of the cortex will be produced, in order to provide direct visualization of patterns of connections within the cortex, and serve as a reference to the 3-D reconstruction for quantitative and statistical analysis of labeling patterns. In addition, the OMPFC of the human brain will be analyzed with several histological and immunohistochemical stains, in order to define architectonic areas and correlate these with the areas previously distinguished in monkeys. This is especially significant because of the increasing use of imaging methods to analyze patterns of activity within the human brain, and the need to correlate these patterns with the architectonic structure of the cortex and with connections that have been defined in non-human primates.